1. Field of the Invention
The invention relates to the use of interleukin 2 to treat cachexia associated with cancer, infectious disease, and other catabolic states.
2. Description of the Background Art
One of the major and most characteristic problems seen in cancer patients is weight loss, usually associated with anorexia. The extensive wasting which results is known as "cachexia." The causes for this commonly observed and often life-limiting disturbance remain to be determined, even though many contributing factors have been identified Mendelsohn, J., Principles of Neoplasta in Harrison's PRINCIPLES OF INTERNAL MEDICINE, 11th Ed., (Braunwald et al., Eds.) McGraw-Hill Book Co., New York, 1987, Chap. 78, pp. 421-431). The cachectic state is associated with significant morbidity and is responsible for the majority of cancer mortality, despite advances in nutritional support. (Fearon, K. C. H. et al., Ann. Surg. 208:1-5 (1988)).
In a review, Kern, K. A. et al. (J. Parent. Enter. Nutr. 12:286-298 (1988)) described cancer cachexia as a syndrome which includes progressive weight loss, anorexia, and persistent erosion of body mass in response to a malignant growth. The fundamental physiological derangement as said to be a decline in food intake relative to energy expenditure. Insulin therapy has been proposed as one way to preserve host composition. However, to date, no successful form of therapy has been found.
A number of studies have suggested that a molecule known alternatively as tumor necrosis factor (TNF), cachectin, or TNF/cachectin, is an important mediator of cachexia in cancer, infectious disease, and other catabolic states. The biology and chemistry of TNF has been reviewed extensively in recent years (Beutler, B. et al., Nature 320:584-588 (1986); Parasitol. Today 3:345-346 (1987); Ann Rev. Immunol. 7:625-655 (1989); Le, J. et al., Lab. Invest. 56:234-248 (1987); Old, L. J., Science 230:630-632 (1985); Nature 326:330-331 (1987); Palladino, M. A., J. Natl Canc. Inst. 81:474-475 (1989); Playfair, J. H. L. et al., Immunol. Today 5:165-166 (1984); Ruddle, N. H., Immunol. Today 8:129-130 (1987); Tracey, K. J. et al., J. Infec. Dis. 157:413-420 (1988 March). Leading experts in the area have recently concluded that our understanding of the role of TNF is too shallow to allow a precise assessment of conditions under which its administration or removal would prove to be of benefit (Beutler, B. et al., Ann Rev. Immunol. 7:625-655 (1989)).
TNF was initially discovered on the basis of its ability to kill tumor cells and shrink tumor mass (hence the name "tumor necrosis factor"). TNF has therefore been tested as an anti-tumor therapeutic agent in pre-clinical trials (see, for example, Nishimura, T. et al., Int. J. Canc. 40:255-261 (1987); Zimmerman, R. J. et al., J. Natl. Canc. Inst. 81:227-231 (1989)) and in clinical studies (see below). The paradoxical discovery that some of the major life-threatening clinical sequelae of cancer are mediated, at least in part, by the very molecule that may be important in host defense against cancer has cast a pall over this area of research. (See, for example, Balkwill, F. et al., Lancet 1229-1232 (1987).